Antibacterial 5-nitrofuryl-pyrimidines

ABSTRACT

WHEREIN R1 and R2 each represent hydrogen, hydroxyl, lower alkyl, alkoxy, amino or acylamino, and R3 is hydrogen, hydroxyl, lower alkoxy, amino or acylamino. The 5-nitrofuran derivatives of the above formula constitute particularly effective antibacterial agents and are particularly useful in the treatment of urinary track infections. Novel 5-nitrofuran derivatives and the physiologically acceptable salts thereof having the formula:

United States Patent lnventors Herbert Berger Mannheim-Kafertal;

Rudi Gall, Grossachsen; Merdes, l-lartmut, Heidelberg; Kurt Stach, Mannheim- Waldhof; Wolfgang Voemel, Mannheim;

Winfriede Sauer, Mannheim-Wallstadt, all

oi Germany Appl. No. 783,715 Filed Dec. 13, 1968 Patented Nov. 16, 1971 Assignee Boehringer Mannheim GmbH Mannheim, Germany Priority Jan. 20, 1968 Germany P 16 70 307 .4

ANTIBACTERIAL S-NITROFURYL-PYRIMIDINES 8 Claims, No Drawings US. Cl 260/251 R, 260/256.4 C, 260/256.4 N, 260/257, 260/260,

Int. Cl C07d 51/38 Field of Search 260/251,

m i termites Cited UNITED STATES PATENTS 3,096,332 7/1963 Von Esch et al Primary ExaminerAlex Mazel Assistant Examiner-R. V. Rush Attorney-Burgess, Dinklage & Sprung ABSTRACT: Novel 5-nitrofuran derivatives and the rbyeisles eeseneP' e l yllergsi ha in hqfisme emf/ wherein R, and R,, which can be the same or different, are each hydrogen, hydroxyl, lower alkyl, alkoxy, amino or acylamino and R is hydrogen, hydroxyl, lower alkoxy, amino or acylamino and the physiologically compatible salts thereof.

It is to be understood that those compounds (I) in which R is hydroxyl can also be present in the tautomeric lactam form.

Tl-Ie novel-S-nitrofuran derivatives (l) according to the present invention are characterized by their antimicrobial action.

In US. Pat. No. 3,096,332, there are disclosed 2-(5-nitro-2- furyl)-pyrimidine derivatives, similar to the compounds of the invention. These compounds possess in vitro a certain activity against bacteria but in animal experiments have proved to be substantially inactive (see J. Med. Chem., 8, 26/ 1965).

in accordance with the invention it has now been found that the new -nitrofuran(l) are not only effective in vitro, but, surprisingly, also possess an outstanding antibacterial action in vivo. The new compounds according to the present invention are, in particular, outstandinglyeffective in the treatment of infections of the urinary tract. a a

The 2-(5-nitro-2-furyl)-pyrimidine derivatives of structural formula (l) in which R is hydrogen, methyl or methoxy, R, is hydrogen, lower alkyl, amino or acetylamino and R is hydroxyl, hydrogen, methoxy or acetylamino or amino have proved to be particularly effective antibacterial agents.

The novel S-nitrofuran derivatives according to the present invention can be prepared, for example, by one of the following methods:

a. Nitration of a furan derivative having the following formula:

5 (III) wherein R represents hydrogen, lower alkyl or alkoxy, R represents hydrogen, lower alkyl or acylamino and R represents hydrogen, hydroxyl or alkoxy or with a functional derivative thereof, whereafter, if desired, the acylamino radical is saponified;

c. When R and R are to designate hydrogen or lower alkyl and R is to designate hydroxyl or lower alkoxy, hydrolysis or alcoholysis of a-9i229rsn s ria 9031s female wherein R and R each represent hydrogen or lower alkyl and X is halogen.

When products are obtained in which one or more of the substituents R R, and R is an amino group, then, if desired, these products can be converted into physiologically compatible salts by reaction with appropriate inorganic or organic acids.

Acid addition salts of the S-nitrofuran derivatives of the invention are formed by contacting the S-nitrofuran derivatives 'with a mineralor organic acid such as hydrochloric acid, sulfuric acid,-formic acid, acetic acid, citric acid, maleic acid, fumaric acid, phosphoric acid, tartaric acid, benzoic acid, cinnamic acid, succinic acid, mandelic acid and so forth.

The nitration of the furan derivatives (ll) is advantageously carried out with a nitration mixture of nitric acid, sulfuric acid and acetic anhydride. Amino groups which are sensitive to oxiidation are thereby simultaneously acetylated and protected 'against attack by the nitric acid. After the nitration has taken place, the N-acetyl groups can, if desired, be split off 'hydrolytically, for example, with methanolic hydrochloric acid. The saponification of any alkoxy radicals which may be present can, if desired, be carried out in the conventional manner for example using a mixture of a hydrohalic acid, such as hydrobromic acid, nd glacial acetic acid. When the N- acetyl compounds are heated for a comparatively long period of time in strongly acidic solution, not only is the acetyl group split off but the amino compounds initially formed are I hydrolyzed to form the corresponding hydroxy compounds.

The condensation according to the present invention of 5- nitro-furamidine with the B-dicarbonyl compounds (lll) is preferably carried out with the use of a basic catalyst, such as 'an alkali metal alcoholate. lt is not known whether the compounds (Ill) thereby react in the keto or enol fonn. Typical functional derivatives of compounds (lll) are the acetals, as well as the enamines and the halo derivatives of the enol form, as for example, fl-chloroacrolein.

In the case of the hydrolysis of compounds ([V), when a a mixture of glacial acetic acid and sodium acetate is used, there are obtained after neutralization, the corresponding 4-hydrox- .y-pyrimidine derivatives. The alcoholysis, which is advantageously carried out in an anhydrous alkali metal alcoholate solution results in the formation of corresponding 4-alkoxy-pyrimidine derivatives.

The furan derivatives (ll) used as starting materials can be prepared, for example, by the reaction of furamidine with appropriately substituted B-dicarbonyl compounds, any free amino groups which may be present advantageously being acylated prior to the condensation. A particularly simple variation of this process makes use of B-carbonyl-carboxylic acid esters or of B-substituted B-dicarboxylic acid esters, the corresponding 2-hydroxyor 2,4-dihydroxy-pyrimidines being thereby initially obtained. These are thereafter converted into the 2-chloroor 2,4-dichloro-pyrimidine derivatives by reaction with an inorganic acid chloride, such as phosphorus oxychloride. The chlorine atoms can then be partially or wholly replaced by hydrogen atoms by means of catalytic hydrogenation or by amino groups by reaction with ammonia or by alkoxy radicals by reaction with alkali metal alcoholates or by hydroxyl groups by reaction with water.

The starting compounds (N) can be obtained by the nitration of those compounds having structural formula (ll) in which R is a halogen atom.

I The especially preferred physiologically compatible salts of the amino group-substituted 2-(5-nitro-2-furyl)-pyrimidine derivatives (1) are the hydrochlorides, sulfates, phosphates, tartrates, citrates and oxalates, these salts being prepared in known manner, for example, by neutralization with the appropriate acids. The following examples will illustrate the 0 present invention without limiting the latter thereto.

2-(5-Nitro-2-furyl)-4-methyl-pyrimidine Five g. 2-(2-furyl)-4-methyl-pyrimidine were suspended in 50 ml. acetic anhydride. A nitration mixture which consisted of 5 g. nitric acid, 70 ml. acetic anhydride and 70 ml. concentrated sulfuric acid was added in dropwise fashion to the resulting suspension under stirring, at a temperature of l C. When the addition of the nitration mixture had been completed, the reaction mixture was stirred for 1 additional hour at the same temperature and then poured onto ice, neutralized and the precipitated crystals filtered off with suction. Following washing and drying, there were obtained 4 g. (62 percent of theory) of paper chromatographically uniform 2-(5-nitro-2-furyl)-4-methyl-pyrimidine which, following recrystallization from alcohol/dimethyl formamide, had a melting point of l98-206 C. The NMR and infrared spectra analyses confirmed the structure of the product.

The 2-( 2-furyl)-4=methyl-pyrimidine used as starting material was prepared by the reaction of furamidine hydrochloride with sodium acetoacetic ester in alcohol, subsequent chlorination with phosphorus oxychloride and catalytic hydrogenation of the 2-(2-furyl)-4-methyl-6- chloropyrimidine (m.p. 3437 C.) obtained as an intermediate. There was obtained an oil which, in the cold, crystallized slowly (m.p. 3538 C.) and the structure of which was confirmed by the NMR spectrum.

The following compounds were obtained in an analogous manner: 2-(S-nitro-Z-furyl)-pyrimidine: m.p. 2 l 42l9 C.

As starting material, there was used 2-(2-furyl)-pyrimidine (m.p. 6669 C.) which had been prepared by the reaction of 2-(2-furyl)-4,6-dihydroxypyrimidine, the'latter obtained according to the method described in J.C.S., 1943, 388, with phosphorus oxychloride, followed by catalytic hydrogenation of the 2-(2-furyl)-4,6-dichloropyrimidine (m.p. 68-71 C.) which was obtained as an intermediate. 2-(5-nitro-2-furyl)-4-methoxy-S-methyl-pyrimidine: l60l65C.

As starting material, there was used 2-(2-furyl)-4-methoxy- S-methyl-pyrimidine (m.p. 798l C.) which had been prepared by the following reaction: 2-(2-furyl)-5-methyl-4- (3H)-pyrimidinone (m.p. 21S-2l7 C.), obtained by the con- As starting material, there was used 2-(2-furyl)-5-methyl-,

pyrimidine: (m.p. 87-90 C.), which had been prepared by the catalytic hydrogenation of 2-( 2-furyl)-4-chloro-5-methylpyrimidine.

2-( 5-nitro-2-furyl)-4-methyl-6-( 1H )-pyrimidinone: 248252 C. (decomp.)

As starting material, there was used 2-(2-furyl)-4-methyl-6- (1H)-pyrimidinone (m.p. 3538 C.)'

2-( 5-nitro-2-furyl)-4,5-dimethyl-6-( lH)-pyrimidinone: 284289C. (decomp.)

As starting material, there was used 2-(2-furyl)-4,5- dimethyl-6-(lH)-pyrimidinone (m.p. 227-232 C.), which had been obtained by the condensation of furamidine hydrochloride with the sodium salt of a-methyl acetoacetic ester in alcohol. 2(S-nitro-2-furyl)-5-ethyl-4-(3H)-pyrimidinone: 224-230C.

As starting material, there was used 2-(2-furyl)-5-ethyl-4- (3H)-pyrimidinone (m.p. l57160 C.), which had been prepared by the condensation of furamidine hydrochloride with the sodium salt of a-formyl butyric acid ethyl ester. 2-(5-nitro-2-furyl)-4,5-dimethylpyrimidine: m.p. l93l96 C.

m.p. 300 C.

-pyrimidinone: (m.p. 200204 C.), which was prepared by the following reaction: lfuramidine hydrochloride was condensed with the sodium slat of malonic acid diethyl ester and the 2-(2-furyl)-4,6-dihydroxy-pyrimidine thereby obtained reacted with phosphorus oxychloride. Following partial hydrolysis of the 2-(2-furyl)-4,6-dichloropyrimidine formed, there was recovered 2-(2-furyl)-4-hydroxy-6-chloropyrimidine (m.p. 239-24l C.). By catalytic hydrogenation of the latter compound there was obtained 2-(2-furyl)-4-(3H)- pyrimidinone. 2-(5-nitro-2-furyl)-4-acetamino-5methyl-pyrimidine: 225C.

As starting material, there was used 2-(2-furyl)-4- acetamino-S-methyl-pyrimidine (m.p. l8l-l82 C.), which had been prepared by the following reaction: furamidine hydrochloride was condensed with the sodium salt of methyl malonic acid diethyl ester and the 2-(2-furyl)-5-methyl-4,6- dihydroxy-pyrimidine thereby obtained reacted with phosphorus oxychloride to give 2-(2-furyl)-5-methyl-4,6- dichloropyrimidine (m.p. 1 l4l 17 C.). Following ammonolysis, at a temperature of C,, using aqueous ammonia, in an autoclave, there was obtained therefrom 2-(2-furyl)-5- methyl-4-amino-6-chloropyrimidine (m.p. 230233 C.). This latter compound was then reacted with acetic anhydride to give 2-(2-furyl)-4-acetamino-5-methyl-6-chloropyrimidine (m.p. l99200 C.). By the catalytic hydrogenation thereof,

there was obtained 2-(2-furyl)-4-acetamino-5-methylpyrimidine. 2-(5-nitro-2-furyl)-5-acetamino-pyrimidine: m.p. 280 C. (decomp.)

As starting material, there was used 2-(2-furyl)-5- acetamino-pyrimidine [m.p. 286 C. (decomp.)], which was obtained by the condensation of furamidine hydrochloride with 2 -nitromalonic dialdehyde, reduction of the 2-(2-furyl)- 5-nitro-pyrimidine (m.p. 240-241 C.) thereby obtained to give 2-(2-furyl)-5-amino-pyrimidine (m.p. l94l97 C.) and subsequent acetylation with acetic anhydride.

EXAMPLE 2 Utilizing the 2-(5-nitro-2-furyl)-4-acetamino-5-methylpyrimidine obtained by the procedure described in example I, there was first obtained the hydrochloride of 2-(5-nitro-2-furyl)-4-amino-5-methyl-pyrimidine by boiling for 1 hour in methanalic solution which had been saturated with hydrogen chloride. Following neutralization with sodium bicarbonate and recrystallization of the product from dimethyl formamide, there was recovered in 68 percent yield, the free amino compound. The 2-(5-nitro-2-furyl)-4-amino-5-methyl-pyrimidine melted, with decomposition at 325330 C.

Using an analogous method, 2-(5-nitro-2-furyl)-5-aminopyrimidine [m.p. 285295 C. (decomp.)] was prepared by the saponification of 2-(5-nitro-2-furyl)-5-acetaminopyrimidine with methanolic hydrochloric acid followed by neutralization of the thusly obtained product.

EXAMPLE3 2-( 5-Nitro-2-furyl)-5-methyl-4-( 3H )-pyrimidinone VariantA:

Five g. 2-(2-furyl)-5-methyl-4-(3H)-pyrimidinone were suspended in 50 ml. acetic anhydride. A nitration mixture which consisted of 3.4 ml. concentrated nitric acid, 50 ml.

acetic anhydride and 50 ml. concentrated sulfuric acid was added in dropwise fashion under stirring, at a temperature of l C. The reaction mixture was then stirred for a further hour at -l0 C., poured onto ice and the precipitated crystals filtered off using suction. After washing and drying, there were obtained 3.7 g. (59 percent of theory) of the paper chromatographically pure nitro compound, the structure of which was confirmed spectroscopically. Following recrystallization from alcohol/dimethyl formamide, the 2-(S-nitro-2-furyl)-5- methyl-4-(3H)-pyrimidinone which was obtained had a melting point of 305-3 15 C. (decomp.)

The 2-(2-furyl)-5-methyl-4-(3H)-pyrimidinone (m.p. 2l52l7 C.) used as starting material was prepared by the condensation of furamidine hydrochloride with the sodium salt of a-formyl-propionic acid ethyl ester.

Variant B:

2.8 g. 2-(5-nitro-2-furyl)-4-chloro-5-methyl-pyrimidine (m.p. l98-l99 C.) in admixture with 2 g. sodium acetate were boiled under reflux in 30 ml. glacial acetic acid until a sample as shown by means of a thin layer chromatogram, evidenced that the starting material had been completely hydrolyzed. Following cooling and neutralizing, the crystals obtained were filtered off with suction, washed and dried. There were thusly obtained 2.1 g. (81 percent of theory) 2-(5- nitro-2-furyl)-5-methyl-4-(3l-l)-pyrimidinone.

The 2-(5-nitro-2-furyl)-4-chloro-5-methyl-pyrimidine used as starting material was prepared by the reaction of 2-(2-furyl)-- methyl-4-(3l-l)-pyrimidinone with phosphorus oxychloride (chloro compound: m.p. l45-l48 C.) followed by nitration of the chloro compound. After recrystallization from dimethyl formamide/water, the product had a melting point of 198- 1 99 C.

Variant C:

2-(5-nitro-2-furyl-4-methoxy-5methyl-pyrimidine which had been prepared by the procedure described in example 1 was heated with 40 percent hydrogen bromide solution in glacial acetic acid. 2-(5-nitro-2-furyl)-5-methyl-4-(3H)- pyrimidinone was thereby obtained in good yield.

Variant D:

One g. 5-nitro-2-furamidine hydrochloride and an equimolar amount of the sodium salt of a-formyl-propionic acid ethyl ester were stirred in absolute alcohol, while heating under reflux. After 2 hours, the reaction mixture was cooled and the precipitate filtered off using suction and washed with water. The 2-(5-nitro-2-furyl)-5-methyl-4-(3l-l)-pyrimidinone thusly obtained was recrystallized from dimethyl formamide/alcohol.'2-(5-nitro-2-furyl)-5-methyl-4-(3H)-pyrimidine having a melting point of 306-315 C. (decomp.) was obtained in a yield of0.25 g.

EXAMPLE 4 2-( 5-Nitro-2-furyl)-5-hydroxy-pyrimidine 0.5 g. 2-(5-nitro-2-furyl)-5-acetamino-pyrimidine prepared 1 by the method described in example 1 was heated with 4 ml.

EXAMPLE 5 The following compounds were prepared in a manner analogous to that described in example 1: 2-(5-nitro-2-furyl)-4-methyl-6-acetamino-pyrimidine: l99204 C. (decomp.)

As starting material, there was used 2-(2-furyl)-4-methyl-6- acetamino-pyrimidine (m.p. l75-l77 C.), which was prepared by the following reaction: 2-(2-furyl)-4-methyl-6- chloropyrimidine was reacted with aqueous ammonia in an autoclave at a temperature of 150 C. The 2-(2-furyl)-4- methyl-6-amino-pyrimidine (m.p. l76-l78 C.) thusly obtained was then heated with acetic anhydride. 2-(5-nitro-2-furyl)-4-acetamino-pyrimidine: m.p. 277-279 Mea an-L. L

As starting material, there was used 2-(2-furyl)-4- acetamino-pyrimidine (m.p. l92-l96 C.) which had been prepared by the following reaction: 2-(2-furyl)-4-(3H)- pyrimidinone was reacted with phosphorus oxychloride to give 2-(2-furyl)-4-chloropyrimidine (m.p. -82 C.). Following the ammonolysis thereof at a temperature of C. with aqueous ammonia in an autoclave, there was obtained 2- (2-furyl)-4-amino-pyrimidine (m.p. l5 l-l54 C.), which was thereafter reacted with acetic anhydride.

EXAMPLE 6 2-( 5-Nitro-2-furyl )-4-methyl-6-amino-pyrimidine In an analogous manner, by the saponification of 2-(5-nitro- 2-furyl)-4-acetamino-pyrimidine, with alcoholic hydrochloride acid and subsequent neutralization, there was obtained 2-(5-nitro-2-furyl)-4-amino-pyrimidine, which had a melting point of 2953 10 C. (decomp.).

The bacteriostatic activity of the compounds in accordance with the invention was evaluated in vitro with respect to the organisms as set out in the following table.

The absolute bacteriostatic minimal concentration was determined for the following compounds of the invention and for four known or comparison compounds as hereinafter set out:

A. 2-(5-nitro-2-furyl)-5-methyl-4(3H)-pyrimidinone B. 2-(5-nitro-2-furyl)-pyrimidine C. 2-(S-nitro-Z-furyl)4,5-dimethyl-6-( lH)-pyrimidinone 2-(5-nitro-2-furyl)-4-methyl-6-( l H )-pyrimidinone (5-nitro-2-furyl)-5-ethyl-4-(3l-l)-pyrimidinone (5-nitro-2-furyl)-4-methyl-pyrimidine -(5-nitro-2-furyl)-4-(3l-l)-pyrimidinone 2-(5-nitro-2-furyl)-4-methyl-6-acetaminc-pyrimidine 2-(5-nitro-2-furyl)-4-methyl-6-amino-pyrimidine 2-(5-nitro-2-furyl)-4-acetamino-pyrimidine 2-(5-nitro-2-furyl)-4-amino-pyrimidine 2-(5-nitro-2-furyl)-5-methyl-pyrimidine 2-(5-nitro-2-furyl)-4-methoXy-S-methyI-pyrimidine 2-(5-nitro-2-furyl)-5-acetamino-pyrimidine 2-(5-nitro 2-furyl)-5-amino-pyrimidine P. 2-(5-nitro-2-furyl)-4-acetamino-5-methyl-pyrimidine Q. 2-( 5-nitro-2-furyl)-5-hydroxy-pyrimidine R. 2-(S-nitro-Z-furyl)-4,6-dimethyl-pyrimidine from US. Pat. No. 3,096,332)

S. Furacin-trade name for nitrofurazone 5-nitro2-furuldehyde-semicarbazone-Eaton Laboratories Norwich, New York T. Furoxon-trade name for furazolidone 3-(5-nitro-furfurylideneamino)-2-oxazolidinone--Eaton Laboratories, Norwich, New York U. Furadantintrade name for nitrofurantoin(N(5- nitro-2-furfurylidene)-l-aminohydantoin)-Eaton Laboratories, Norwich, NY.

The results are set out in the following table:

(known wQ mm Amos R E $22 wa Nm fiwmv SEE S 238 wNH 2 QKQ @QBENE 333 wmfi 3 Q S .FEEQE 352m EH m 8 8 53; 252

wmA mmA fiwmv Su .m Efi ak 3A wwA 3 305223 w efiqguwm fifi 3 2S 32:3:3 Sw

wNHA 3 68 2 535% fiegfim mm mm o w $5 85223 $322 w mm c w 28 5383: 33M mfim mmko m mm" d m 82v :8 tufi w amma q 3H 0 m AwC :8 zttwfinw EEO w N w 8n: a ma 2838325 w w 2 N N 2 w Q V QQEC SEES E w nfl o w I m A58 2855 338083523 oktwon N w w w w M w 9 w 3 H N u H w v w 2 E w w as In mm .32? si fi w v D a w m Q m o .A E a M H H m o m m m o m 5 0 Em mmH BE: 5 93 5538 555 23325 2 338n in addition, the following compounds were evaluated with respect to their bacteriostatic activity in urine of rats following oral administration. The result of this experiment are set out in table 11 which follows:

corporation into a water-soluble ointmentlike base (concentration 01-05 percent or in a powder base composed for instance of water-soluble polyethylene glycols (concentration 0.1-0.5 percent); or in a form suitable for ingestion. Thus, a

TABLE 11.BACTER1()STATIC ACTIVITY OF THE URINE AND OF THE EXCRETED AMOUNT OF ACTIVE SUBSTANCE IN THE URINE OF RATS FOLLOWING ORAL ADMINISTRATION lincterlostetic maximum dilution of urine ugninst Escherichia 0011' (106) determined in 50 m1. urine sumples .22 hours utter me. test. compound per kg. body Weight had been orully miministered. Ii rets were employed for each experiment and every value recorded In the tnble represents the results thereby olitaine urine (in percent administered).

(1. 'lhe snme experiment with the amount of antibacterial active substance excreted in the A o 1) E Q Q The acute oral toxicity was determined in mice. the results 2 preferred form is a tablet containing 50-200 mg. of active are shown in table 111.

TABLE 111 COMPOUND Furadantin (u') Furadantin (u) OOWOO Published 'vaTtETQEI" 2 Unpublished value 1968 As can be seen from table 111, the toxicity of the compounds of the invention is lower than that of furadantin. While the bacteriostatic activity of both the known and novel compounds is quite similar, the novel compounds have a much better activity in vivo as compared to the known comparison compounds.

The compounds in accordance with the instant invention are anti-microbials and have been found to be bactericidal to the pathogens found in surface infections, gram negative as well as gram positive. They additionally have utility as agents for routine treatment of acute and chronic bacterial infections of the urinary tract, including those caused by Proteus ap. Further they lend themselves because of their properties to use in the prevention of treatment of mixed surface infections of wounds, severe burns, cutaneous ulcers, pyodermas, osteomyelitis, preparation of wounds and burns for skin grafting and prevention of infection of grafts and donor sites.

The compounds of the invention can be employed in the form of aqueous solutions or suspensions thereof, as for instance, in the form of an 0.01-0.05 percent aqueous suspen-' sion or solution; in the form of solutions in nonaqueous, hygroscopic liquid vehicles such as polyethylene glycol, for instance, 01-05 percent solutions in polyethylene glycol; in-

compound. Depending on the condition, symptomatic and laboratory responses -400 mg. per day can be administered. Another preferred form or orally administering the compounds of the invention is in the form of a suspension thereof in a water miscible flavored gel. Such a gel can contain from 1-10 mg. ofcompound per cc.

We claim:

1. S-nitrofuran derivative and nontoxic acid addition salts thereof, said nitrofuran derivative having the formula:

in which R and R each represent a member selected from the group consisting of hydrogen, hydroxyl, lower alkyl, lower alkoxy, amino and acetylamino and R is a member selected from the group consisting of hydrogen, hydroxyl, lower alkoxy, amino and acetylamino; wherein at least one of the radicals R R and R is hydroxyl. I

2. Compound as claimed in claim 1 wherein only one of R R and R is hydroxyl.

3. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-5-methyl-4-(31-1)-pyrimidinone.

4. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-4,5-dimethyl-6-( 11'1)-pyrimidinone.

5. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-4-methyl-6-( 1H)-pyrimidinone.

6. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-5-ethyl-4-(31-1)-pyrimidinone.

7. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-4-(31-1)-pyrimidinone.

8. A compound according to claim 1 designated 2-(5-nitro- 2-furyl)-5-hydroxy-pyrimidine.

Novemwr 15, 1971 Inventofls) deli-bet? Berger Rucii Gem Katmai Merdjes,

Wolfgang Voemei and Wimfriefie Seuer Kurt Stach,

it is certified that error appears in the above-identified patent and that said; Letters Patent are hereby corrected as: shown below:

Aiwtract last lijfi "track" siwuld be --tract-- nlq 1, line 73 (Spee. p. line 7) R {seccmfl eccugrence} sheuld be a fine 12 (Spec. p. 16, line 1 C u i "e'iet" e'haul %e "salt-' CnL, 1%, line 1 {Spam p. 28, line 23) *niaebawntlike ahould be --eintment-1ike-a and sealed this 23rd 

2. Compound as claimed in claim 1 wherein only one of R1, R2 and R3 is hydroxyl.
 3. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-5-methyl-4-(3H)-pyrimidinone.
 4. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-4,5-dimethyl-6-(1H)-pyrimidinone.
 5. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-4-methyl-6-(1H)-pyrimidinone.
 6. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-5-ethyl-4-(3H)-pyrimidinone.
 7. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-4-(3H)-pyrimidinone.
 8. A compound according to claim 1 designated 2-(5-nitro-2-furyl)-5-hydroxy-pyrimidine. 